Objective To explore the pathological mechanism of brain function and structure in young patients with major depressive disorder by diffusion tensor imaging(DTI)and resting state functional magnetic resonance imaging(fMRI).Methods Sixteen participants diagnosed with major depression (MD) and 16 healthy age and gender-matched controls(HC) were recruited. Resting state fMRI and DTI brain scans were performed on all participants. A voxel-based method (VBM) was used to analyze the DTI datasets, and regional homogeneity (ReHo) approach was applied to preprocess the fMRI datasets. The value of fractional anisotropy (FA) and ReHo maps were obtained in the whole brain.Results FA values in the MD group were significantly lower than those of the healthy controls in the white matter of the left middle temporal gyrus, right middle frontal gyrus, left medial frontal gyrus, right precentral gyrus, left angular gyrus, left fusiform gyrus, left superior temporal gyrus, right middle temporal gyrus, right sub-gyral, left insula, and left pyramis (P＜0.01). ReHo in the MD group decreased in the left superior frontal gyrus, right superior frontal gyrus, left middle frontal gyrus, right middle frontal gyrus, left medial frontal gyrus, right medial frontal gyrus, left paracentral lobule, right paracentral lobule, right inferior parietal lobule, left postcentral gyrus, right postcentral gyrus, left middle occipital gyrus, left lingual gyrus, right putamen, right cingulate gyrus, right cuneus, left superior temporal gyrus, and right middle temporal gyrus (P＜0.01). Conclusion Abnormality of brain white microstructure and function exist widely in young patients with major depressive disorder. Abnormal connection of structures and function between the brain areas may be the key reason for the depression.

Objective To evaluate the diagnostic performance of diffusion kurtosis imaging (DKI) and its combination with DWI and proton MR spectroscopy (1H-MRS) in differentiating malignancy from benign breast lesions. Methods Fifty-three patients with 38 histopathologically confirmed malignant and 15 benign breast lesions were retrospectively studied. The patients were examined by breast MRI at 3.0 T prior to operation, including conventional T1WI, fat-suppression imaging, DWI, DKI and 1H-MRS. The shape and margin of breast lesions, and their corresponding mean values for ADC, mean kurtosis (MK) and mean diffusivity (MD) were determined by two blinded radiologists in consensus. The presence or absence of choline (Cho) peak was identified using LCModel software. Independent-samples t test or χ2 test was performed for the comparison of clinical characteristics, shape and margin of lesions, and imaging parameters between malignancy and benign lesions. ROC analysis was performed to evaluate the diagnostic accuracy of DKI, DWI and 1H-MRS alone or in combination, in comparison with the histopathologic findings. Results The onset age of breast malignancy was higher than that of benign ones, and the difference has statistical significant (P<0.05). Malignant lesions were most often seen in postmenopausal women, with unclear margin. There was no significant differences for body mass index (BMI), fiber type, the size and shape of lesions between benign lesions and malignancy (P>0.05). The mean ADC,MD and MK of benign lesions were(1.464 ± 0.348)× 10-3mm2/s,(1.726 ± 0.268)× 10-3mm2/s and(0.692 ± 0.227), the mean ADC,MD and MK of malignancy were(0.963 ± 0.170)× 10-3mm2/s,(1.158 ± 0.262)× 10-3mm2/s and(1.311 ± 0.218), respectively. Significant differences were obtained between benign and malignant lesions for all parameters (P<0.05).The area under the ROC curve (AUC) of ADC, MD and MK for differentiating malignancy from benign lesions was 0.913, 0.933 and 0.968, respectively. Taken the maximum Youden's index of MK (1.110) as the ROC optimal cut-off point, MK exhibited better diagnostic sensitivity, specificity and accuracy for distinguishing malignancy from benign lesions [89.5%(34/38),93.3%(14/15) and 90.6%(48/53), respectively], compared with MD and ADC. Multiparametric imaging with combination of DKI, DWI and 1H-MRS improves the diagnostic specificity (with the highest as 100.0%) but decreases the sensitivity (with the highest as 81.6% and lowest as 71.1% ), compare with the single parametric imaging. Conclusions MK generated from DKI enables differentiation of breast lesions with a higher diagnostic sensitivity and specificity than DWI and 1H-MRS. DKI combined with DWI and 1H-MRS increase specificity but decrease sensitivity for breast cancer characterization.

Objective To explore the effect of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism,environmental factor and their interactions on antidepressant treatment.Methods 340 patients of major depressive disorder (MDD) who met the diagnosis criteria of MDD ( DSM-Ⅳ Axis Ⅰ) were recruited.280 patients of them were finished 12 weeks antidepressant treatment.The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS) before and after 12 weeks antidepressant treatment.Childhood Trauma Questionnaire,28-item Short Form (CTQ-SF) and Life Events Scale (LES) were used to evaluate childhood adverse and life stress before onset.Genotyping of BDNF Val66Met polymorphism was detected by Illumina GoldenGate assays.Results Male patients proportion were significantly higher in non-remitters than remitters (P =0.008 ).After adjusting by gender, the frequencies of genotype and allele for the BDNF Val66Met polymorphism were no significant difference between remitters (AA: AG: GG = 28: 79: 40, A:G = 135:159 ) and non-remitters (AA: AG: GG = 29:81:23 ,A: G = 139:127 ) (P ＞0.05 ).There was no significant difference of CTQ scores and LES scores between the two groups (P＞0.05 ).The regression analysis showed that social intercourse problem and age were the risk factor for the severity of depression.The gender, HDRS baseline scores and mental disorder family history were associated with the efficacy of 12 weeks antidepressant.However,there was no significantly relationship between the interaction of BDNF Val66Met polymorphism and environment with the antidepressant treatment.Conclusion The older men with the mental disorder family history, severe depression symptom would be less-response to antidepressant treatment.However, BDNF Val66Met polymorphism, childhood trauma, life events stress and the interaction of BDNF Val66Met polymorphism and environment have no significantly effect on the 12 weeks antidepressant treatment.

Objective To characterize the biomarkers of urine samples for early diagnosis of colorectal cancer(CRC)using proton nuclear magnetic resonance (1H-NMR)combined with pattern recognition.Methods 400 MHz 1H-NMR was used to test the urine samples obtained from 23 patients with Ⅰ/Ⅱ stage CRC,40 healthy controls (HC)and 18 patients with esophageal cancer (EC). Pattern recognition through orthogonal partial least squares-discriminant analysis (OPLS-DA)was applied on 1H-NMR data to find urine metabolic differences between CRC and HC.Results OPLS-DA could effectively determine HC,patients withⅠ/Ⅱstage CRC and patients with esophageal cancer.Compared with HC,early stage CRC had significant decreases of choline,isocitric acid,lactamine,phenylalan, cysteine,creatinine,aspartic acid,hippurate acid,methylamine,dimethyl sulfone,and increases of acetoacetate,glutamine,glycocyamine,cis-aconitate, trans-aconitate,homocycteine in the urine samples.Conclusion Urine metabonomics based on NMRIndicates that glucose metabolism,amino acid metabolism,choline metabolism,energy metabolism and intestinal microflora are disturbance in colorectal cancer patients,which provide valuable metabolic information on the molecular level for early diagnosis of colorectal cancer.

Objective To characterize the metabolic "fingerprint" of fecal extracts for diagnosis of early-stage colorectal cancer (CRC) using proton nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics coupled with pattern recognition.Methods From January 2014 to December 2014,we collected fecal samples at the Second Affiliated Hospital of Shantou University Medical College,from 25 patients with colorectal adenomas (CR-Ad),20 with stage Ⅰ /Ⅱ CRC,and 32 healthy controls (HCs).The patients were diagnosed by histopathology.No subjects had any complicating diseases.HCs showed no abnormalities from blood tests,endoscopic examination,diagnostic imaging,and/or medical interviews.We excluded participants who used antibiotics,NSAIDS,statins,or probiotics within two months of study participation,and any patients who underwent chemotherapy or radiation treatments prior to surgery.We used orthogonal partial least-squares-discriminant analysis (OPLS-DA) for pattern recognition (dimension reduction) on 1H-NMR processed data (1H frequency of 400.13 MHz),to find metabolic differences among CR-Ad,carcinoma and HC fecal samples;and receiver operating characteristic (ROC) analysis to determine the diagnostic value of the fecal metabolic biomarkers.Results Fecal samples were collected from 20 patients with Stage Ⅰ/Ⅱ CRC (11 M,9 F,median age (52±13) years),25 with CR-Ad (14 M,11 F,median age (53±11) years) and 32 HCs (15 M,17 F,median age (53± 14) years).OPLS-DA clearly distinguished CR-Ad and stage Ⅰ/Ⅱ CRC from HC samples,based on their metabolomic profiles.Relative signal intensities in HCs were significantly lower than in the cancer patients for butyrate (HC:23.0±6.0;CR-Ad:18.0±5.0;CRC:14.0±6.0;Z=-2.07,P=0.008),acetate (HC:45.0± 11.0;CR-Ad:31.0±11.0;CRC:24.0±8.0;Z=-2.32,P=0.011),propionate (HC:26.0 ± 7.0;CR-Ad:22.0 ± 6.0;CRC:19.0 ± 5.0;Z=-2.43,P=0.032),glucose (HC:37.0±7.0;CR-Ad:31.0±7.0;CRC:26.0±8.0;Z=-2.07,P=0.044) and glutamine (HC:4.5±2.0;CR-Ad:4.9 ± 1.0;CRC:5.4 ± 1.0;Z=2.21,P=0.044).However,relative signal intensities in HCs were significantly higher than in patients for lactate (HC:4.8± 1.0;CR-Ad:6.9±2.0;CRC:4.8± 1.0;Z=2.02,P=0.038),glutamate (HC:3.2±2.0;CR-Ad:4.9 ± 1.0;CRC:3.2± 2.0;Z=2.21,P=0.044) and succinate (HC:12.0±2.0;CR-Ad:15.0±3.0;CRC:12.0± 2.0;Z=2.25,P=0.011).Among the potential biomarkers,acetate at 1.92 ppm,and succinate at 2.41 ppm displayed relatively high area under ROC,with sensitivity and specificity both ＞90％,to distinguish early-stage CRC patients from HCs.Conclusion Fecal metabolic profiles distinguish of HCs from patients with CRC patients,even in the early stages (stage Ⅰ/Ⅱ),highlighting the potential of NMR-based fecal metabolomic fingerprinting as tools for early CRC diagnosis.

Objective To characterize the metabolic "fingerprint" of fecal extracts for diagnosis of early-stage colorectal cancer (CRC) using proton nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomics coupled with pattern recognition.Methods From January 2014 to December 2014,we collected fecal samples at the Second Affiliated Hospital of Shantou University Medical College,from 25 patients with colorectal adenomas (CR-Ad),20 with stage Ⅰ /Ⅱ CRC,and 32 healthy controls (HCs).The patients were diagnosed by histopathology.No subjects had any complicating diseases.HCs showed no abnormalities from blood tests,endoscopic examination,diagnostic imaging,and/or medical interviews.We excluded participants who used antibiotics,NSAIDS,statins,or probiotics within two months of study participation,and any patients who underwent chemotherapy or radiation treatments prior to surgery.We used orthogonal partial least-squares-discriminant analysis (OPLS-DA) for pattern recognition (dimension reduction) on 1H-NMR processed data (1H frequency of 400.13 MHz),to find metabolic differences among CR-Ad,carcinoma and HC fecal samples;and receiver operating characteristic (ROC) analysis to determine the diagnostic value of the fecal metabolic biomarkers.Results Fecal samples were collected from 20 patients with Stage Ⅰ/Ⅱ CRC (11 M,9 F,median age (52±13) years),25 with CR-Ad (14 M,11 F,median age (53±11) years) and 32 HCs (15 M,17 F,median age (53± 14) years).OPLS-DA clearly distinguished CR-Ad and stage Ⅰ/Ⅱ CRC from HC samples,based on their metabolomic profiles.Relative signal intensities in HCs were significantly lower than in the cancer patients for butyrate (HC:23.0±6.0;CR-Ad:18.0±5.0;CRC:14.0±6.0;Z=-2.07,P=0.008),acetate (HC:45.0± 11.0;CR-Ad:31.0±11.0;CRC:24.0±8.0;Z=-2.32,P=0.011),propionate (HC:26.0 ± 7.0;CR-Ad:22.0 ± 6.0;CRC:19.0 ± 5.0;Z=-2.43,P=0.032),glucose (HC:37.0±7.0;CR-Ad:31.0±7.0;CRC:26.0±8.0;Z=-2.07,P=0.044) and glutamine (HC:4.5±2.0;CR-Ad:4.9 ± 1.0;CRC:5.4 ± 1.0;Z=2.21,P=0.044).However,relative signal intensities in HCs were significantly higher than in patients for lactate (HC:4.8± 1.0;CR-Ad:6.9±2.0;CRC:4.8± 1.0;Z=2.02,P=0.038),glutamate (HC:3.2±2.0;CR-Ad:4.9 ± 1.0;CRC:3.2± 2.0;Z=2.21,P=0.044) and succinate (HC:12.0±2.0;CR-Ad:15.0±3.0;CRC:12.0± 2.0;Z=2.25,P=0.011).Among the potential biomarkers,acetate at 1.92 ppm,and succinate at 2.41 ppm displayed relatively high area under ROC,with sensitivity and specificity both ＞90％,to distinguish early-stage CRC patients from HCs.Conclusion Fecal metabolic profiles distinguish of HCs from patients with CRC patients,even in the early stages (stage Ⅰ/Ⅱ),highlighting the potential of NMR-based fecal metabolomic fingerprinting as tools for early CRC diagnosis.

Kirsten rat sarcoma viral oncogene homolog(KRAS)is a type of gene closely related to human tumors.And it's an important medical index to access the tumor development,prognosis and the efficacy of chemoradiotherapy.RAS mutations,in which KRAS mutations account for up to 85%,are the most common oncogenic driving mutations in human tumors.The most frequent KRAS mutation sites are codons 12,13,61 and 146.Codon G12,as the most frequently mutated one,can be divided into multiple subtypes,with G12D mutation being the most common,followed by G12V,G12C,etc.Colorectal cancer(CRC)is one of the tumors with the highest frequency of KRAS mutations.Both G12D and G12V are the most common mutation subtypes in CRC.In the field of treatments for CRC with KRAS mutations,targeted therapy had not been possible until the release of KRASG12C inhibitors in 2013,and new drugs have been developed one after another since then.This study summarized the mutations of KRAS and the advances in clinical research,including the latest advances in targeted drugs,chemotherapy drugs,immunotherapy drugs,ferroptosis,and other treatment methods.Among them,in terms of targeted drugs,this review explored KRASG12C inhibitors(sotorasib,adagrasib,D-1553,IBI351,etc.),anti-angiogenic drugs(monoclonal antibodies such as bevacizumab,remdesizumab,etc),small molecule multi-target tyrosine kinase inhibitors such as sunitinib,etc.In terms of immunotherapy drugs,there have also been many advances,such as the ARETHUSA clinical trial,which found that temozolomide reduced the tumor mutational burden(TMB)of O-6-methylguanine-DNA methyltransferase(MGMT)deficiency and RAS mutation in patients with advanced metastatic colorectal cancer(mCRC),providing innovative ideas for patient immunotherapy.For example,the combination of xindilimab with bevacizumab,oxaliplatin,and capecitabine can be used for first-line treatment of RAS mutations,microsatellite stability(MSS),and unresectable mCRC.Relevant studies have shown that the combination therapy has good therapeutic potential and controllable tolerability safety.This review explored the mechanisms of KRAS mutations and the latest advances in clinical research and treatment,in order to provide reference for the treatment of KRAS mutated colorectal cancer.